17-7674238-C-G
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000546.6(TP53):c.725G>C(p.Cys242Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000546.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
Li-Fraumeni syndrome 1 Pathogenic:1
This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 7791795, 10713666]. This variant is expected to disrupt protein structure [Myriad internal data]. -
Li-Fraumeni syndrome Uncertain:1
This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 242 of the TP53 protein (p.Cys242Ser). This variant is present in population databases (rs121912655, gnomAD 0.003%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 30918304). ClinVar contains an entry for this variant (Variation ID: 647334). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. Experimental studies have shown that this missense change affects TP53 function (PMID: 9405613, 10713666, 17170001, 19681600, 20407015). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at